The primary objective of this proposal is to characterize more fully when and why stress-prone individuals, compared to others, are more likely to experience larger increases in stress-related forms of negative affect when they quit smoking. Evidence suggests that stress-prone individuals focus their attention on cues associated with potential stressors and that nicotine may alter attentional processes in such a manner as to reduce subjective stress (negative affect). Thus, it is hypothesized that nicotine acts as a form of serf-medication for stress-prone individuals because it attenuates attentional bias to stressors (cue predicting aversive events and negative emotional stimuli), thereby decreasing negative emotional states (subjective stress). This attenuation of negative attentional bias and associative processing by nicotine is hypothesized to result from nicotine's enhancing attentional and associative bias to positive and neutral stimuli that in turn compete with and inhibit negative affect-related processing. That is, nicotine is predicted to enhance the salience of neutral and positive stimuli and to reduce the salience of negative stimuli. Nicotine-induced attentional and associative biasing is hypothesized to occur most strongly in situations where the subject has a significant degree of freedom of attentional choice. Thus, the effects of attentional choice (two-picture/movie viewing with one stressful and one neutral or positive alternative) versus no-choice (one stressful picture/movie viewing with no alternative) conditions on nicotine's ability to reduce negative affect will be assessed by presenting blocks with a series of single or dual pictures/mini-movies on a computer monitor. Mood will be assessed before and after each picture/mini-movie series block. In the no-choice task, single pictures will be presented centrally on the computer screen. In the choice task, dual picture images or mini-movies will be presented simultaneously in the left and right visual field. In the choice condition, subjects will be instructed to allocate as much or little of their gaze time to a given picture/mini-movie, but to always be gazing at one of two pictures/movies, in the no-choice condition, subjects will be required to gaze at each picture for the duration of its presentation. Neutral or positive pictures/movies will be interspersed in both the choice and no-choice tasks. Eye-gaze patterns during the choice task and no-choice task will be obtained with an infrared, computerized tracking system. In the choice task, maximal stress-reducing effects of nicotine are predicted to occur during blocks with a high frequency of negative pictures. Nicotine is predicted to reduce gaze directed toward negative pictures and to enhance attention to positive pictures. In the no-choice task, nicotine is expected to have maximal dysphoria-reducing effects when a low frequency of negative pictures is combined with intervening positive pictures. Potential moderating influences of gender, history of traumatic and chronic stress, and individual differences in trait anxiety, depression, and anhedonia will be assessed with regression analyses. This work will use new experimental procedures and technologies, including the precise assessment of individual differences in continuously monitored eye-gaze patterns with an infrared, computerized tracking system. The new knowledge derived from these studies will be useful in developing empirical model-based treatment strategies aimed at increasing smoking abstinence. An EEG stress response index (alpha asymmetry) will be used in a subgroup of subjects during each of the 3 proposed studies.